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OBJECTIVE: To understand the characteristics of cervical lymph node metastasis in Oropharyngeal Squamous Cell Carcinoma (OPSCC) patients, explore the risk factors for lymph node metastasis, and its impact on prognosis. METHODS: Retrospective cohort study. Statistical analysis of the relationship between various clinicopathological factors and lymph node involvement, as well as the independent risk factors affecting lymph node metastasis and their impact on prognosis. RESULTS: The cervical lymph node metastasis rate in this group was 89.2%, with the palatine tonsils and base of the tongue more prone to cervical lymph node metastasis (p=0.007); lower pathological differentiation of OPSCC was more likely to develop cervical lymph node metastasis (p=0.017). The P16 protein positive rate in this group was 58.8%. P16 protein expression did not affect the incidence rate of cervical lymph node metastasis in OPSCC (p=1.000) but influenced the risk of multiple lymph node metastases (p=0.011) and was a risk factor affecting the prognosis of OPSCC (p=0.003). However, the lymph node metastasis status did not affect the survival time of OPSCC patients. CONCLUSION: In the Shanxi region of China, HPV-related OPSCC accounts for a higher proportion; OPSCC has a high rate of cervical lymph node metastasis, but lymph node metastasis does not significantly increase the mortality risk of OPSCC patients, which may be related to the unique characteristics of HPV-related OPSCC. LEVEL OF EVIDENCE Ⅳ: Retrospective cohort study.

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Abstract Objective: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. Methods: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. Results: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). Conclusion: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

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OBJECTIVE: Signs and symptoms of osteomyelitis or septic arthritis in neonates and infants are often nonspecific and early-stage bone infections in infants may often go unnoticed. The objective of this study was to analyze the clinical characteristics of newborns and infants with osteomyelitis and septic arthritis to improve understanding of the disorder and to assist clinicians with diagnosis. METHODS: A retrospective multicenter study was conducted on neonates (0-28 days old, n = 94) and infants (1-12 months old, n = 415) with osteoarticular infections. Data consisting of clinical characteristics, complications, laboratory outcomes, and the pathogenic microorganisms causing osteomyelitis were tabulated. The statistics were further broken down into two regions and the significant differences between neonates and infants were evaluated and compared to the literature. RESULTS: Compared to infants, neonates had significantly lower incidences of fever (p < 0.0001), higher incidences of localized swelling (p = 0.0021), higher rate of infection at the humerus (p = 0.0016), higher percentage of Escherichia coli (p < 0.0001) and Klebsiella pneumoniae (p = 0.0039) infections, lower percentage of Staphylococcus aureus infections (p < 0.0001) and were more likely to develop septic arthritis (p < 0.0001). CONCLUSION: Distinct differences were found between neonatal and infants with osteoarticular infections. Future studies should focus on improving diagnosis and subsequent treatment regimens for younger age groups.

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BACKGROUND: Peritoneal metastasis (PM) is an important factor contributing to poor prognosis in patients with gastric cancer (GC). Transcriptomic sequencing has been used to explore the molecular changes in metastatic cancers, but comparing the bulk RNA-sequencing data between primary tumors and metastases in PM studies is unreasonable due to the small proportion of tumor cells in PM tissues. METHODS: We performed single-cell RNA-sequencing analysis on four gastric adenocarcinoma specimens, including one primary tumor sample (PT), one adjacent nontumoral sample (PN), one peritoneal metastatic sample (MT) and one normal peritoneum sample (MN), from the same patient. Pseudotime trajectory analysis was used to display the process by which nonmalignant epithelial cells transform into tumor cells and then metastasize to the peritoneum. Finally, in vitro and in vivo assays were used to validate one of the selected genes that promote peritoneal metastasis. RESULTS: Single-cell RNA sequencing showed that a development curve was found from normal mucosa to tumor tissues and then into metastatic sites on peritoneum. TAGLN2 was found to trigger this metastasis process. The migration and invasion capability of GC cells were changed by downregulating and upregulating TAGLN2 expression. Mechanistically, TAGLN2 might modulate tumor metastasis via alterations in cell morphology and several signaling pathways, thus promoting epithelial-mesenchymal transition (EMT). CONCLUSIONS: In summary, we identified and validated TAGLN2 as a novel gene involved in GC peritoneal metastasis. This study provided valuable insight into the mechanisms of GC metastasis and developed a potential therapeutic target to prevent GC cell dissemination.

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Abstract Improving vaccine immunity and reducing antigen usage are major challenges in the clinical application of vaccines. Microneedles have been proven to be painless, minimally invasive, highly efficient, and have good patient compliance. Compared with traditional transdermal drug delivery, it can effectively deliver a large-molecular-weight drug into the skin, resulting in a corresponding immune response. However, few studies have examined the relationship between microneedle loading dose and immune effects. In this study, the hyaluronic acid (HA) conical and pyramidal dissolving microneedles were prepared by the two-step vacuum drying method, respectively. The model drug ovalbumin (OVA) was added to HA to prepare dissolving microneedles with different loading amounts. The mass ratios of HA to OVA were 5:1, 5:3, and 5:5. The mechanical properties of the dissolving microneedles were characterized using nanoindentation and in vitro puncture studies. The immune effects of the matrix and drug content were studied in Sprague-Dawley (SD) rats. Finally, the diffusion behavior of OVA and the binding mode of HA and OVA in the microneedles were simulated using Materials Studio and Autodocking software. The experimental results showed that the conical microneedles exhibited better mechanical properties. When the mass ratio of HA to OVA was 5:3, the immune effect can be improved by 37.01% compared to subcutaneous injection, and achieved a better immune effect with relatively fewer drugs. This conclusion is consistent with molecular simulations. This study provides theoretical and experimental support for the drug loading and efficacy of microneedles with different drug loadings

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Introduction: The clinical translation of biofluid markers for dementia requires validation in diverse cohorts. The study goal was to evaluate if blood biomarkers reflecting diverse pathophysiological processes predict disease progression in Mexican American adults. Methods: Mexican American adults (n = 745), 50 years of age and older, completed annual assessments over a mean of 4 years. Serum collected at baseline was assayed for total tau, neurofilament light (NFL), ubiquitin carboxyl-terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation 14 (sCD14), and chitinase-3-like protein 1 (YKL-40). Results: Higher GFAP and NFL were associated with global cognitive decline. Only GFAP was associated with increased incident dementia risk (hazard ratio: 1.611 (95% confidence interval: 1.204-2.155)) and inclusion of additional biomarkers did not improve model fit. Discussion: Among a panel of six blood biomarkers previously associated with neurodegenerative disease, only GFAP predicted incident dementia in our cohort. The findings suggest that blood GFAP levels may aid dementia-risk prediction among Mexican American adults.

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Resumo Fundamento Doenças cardiovasculares são a principal causa de morte na China. Entretanto, os esforços atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insuficiência cardíaca (IC) estão direcionados principalmente para a mortalidade durante a internação e a mortalidade após 30 dias nos Estados Unidos. Dessa forma, é necessário um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cirúrgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagnóstico de IC. Objetivo Identificar variáveis que podem prever a mortalidade por IC um ano após a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no período de um ano. Métodos No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de derivação e um grupo de amostra de teste. O método de simulação Monte Carlo via Cadeias de Markov foi usado para identificar variáveis que podem prever a mortalidade um ano após a alta hospitalar. Variáveis com uma frequência >1% na análise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para análises de modelagens posteriores. A probabilidade posterior de que uma variável estava estatística e significativamente associada ao resultado foi calculada como o número total de vezes em que o IC de 95% da variável não coincidiu com 1 (ou seja, o ponto de referência), dividido pelo número total de iterações. Uma variável com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi incluída na lista final de variáveis. O nível de significância estatística adotado foi 5%. Resultados Cinco variáveis que pudessem prever de maneira robusta a mortalidade um ano após a alta hospitalar foram identificadas: idade, sexo feminino, escore da New York Heart Association (Associação de Cardiologia de Nova Iorque) >3, diâmetro do átrio esquerdo, e índice de massa corporal. Os modelos de derivação e de teste tiveram uma área de curva característica de operação do receptor de 0,79. Essas variáveis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC após um ano, e este foi dividido em três grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes. Conclusão Um escore de risco de 5 variáveis simples pode ser utilizado para avaliar a mortalidade um ano após a alta hospitalar de pacientes internados com IC.

Abstract Background Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF. Objective To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year. Methods In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of >1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable's 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%. Results Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score >3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths. Conclusion A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.

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BACKGROUND: Cardiovascular diseases are the leading causes of death in China. However, present efforts to identify the risk factors for death in patients hospitalized with heart failure (HF) are primarily focused on in-hospital mortality and 30-day mortality in the United States. Thus, a model similar to the model used for predicting the risk in patients considered for cardiovascular surgical procedures is needed to evaluate the risk of the patients admitted with a diagnosis of HF. OBJECTIVE: To identify variables that can predict post-discharge one-year HF mortality and develop a risk score to assess the risk of dying within one year. METHODS: In the present study, 1,742 Chinese patients with HF were randomly divided into two groups: a derivation sample group and a test sample group. A Markov Chain Monte Carlo simulation method was used to identify variables that can predict the one-year post-discharge mortality. Variables with a frequency of >1% in the bivariate analysis and that were considered clinically meaningful were eligible for further modeling analyses. The posterior probability that a variable was statistically and significantly associated with the outcome was calculated as the total number of times that the variable's 95% CI did not overlap with 1 (i.e., the reference point) divided by the total number of iterations. A variable with a probability of 0.9 or higher was considered a robust risk factor for predicting the outcome, and this was included in the final variable list. The level of statistical significance adopted was 5%. RESULTS: Five variables that could robustly predict the one-year post-discharge mortality were identified: age, female gender, New York Heart Association functional classification score >3, left atrial diameter, and body mass index. Both derivation and test models had a receiver operating curve area of 0.79. These selected variables were used to assess the one-year HF mortality risk score, and these were divided into three groups (low, moderate, and high). The high-risk group corresponds to nearly 86% of the deaths, while the moderate group corresponds to 12% of the deaths. CONCLUSION: A simple 5-variable risk score can be used to assess the one-year post-discharge mortality of hospitalized Chinese patients with HF.

FUNDAMENTO: Doenças cardiovasculares são a principal causa de morte na China. Entretanto, os esforços atuais para se identificar os fatores de risco de morte em pacientes hospitalizados com insuficiência cardíaca (IC) estão direcionados principalmente para a mortalidade durante a internação e a mortalidade após 30 dias nos Estados Unidos. Dessa forma, é necessário um modelo semelhante ao modelo utilizado para prever o risco considerado para procedimentos cirúrgicos cardiovasculares em pacientes para avaliar o risco de pacientes internados com diagnóstico de IC. OBJETIVO: Identificar variáveis que podem prever a mortalidade por IC um ano após a alta hospitalar, e desenvolver um escore de risco para avaliar o risco de morte no período de um ano. MÉTODOS: No presente estudo, 1.742 pacientes chineses com IC foram divididos aleatoriamente em dois grupos: um grupo de amostra de derivação e um grupo de amostra de teste. O método de simulação Monte Carlo via Cadeias de Markov foi usado para identificar variáveis que podem prever a mortalidade um ano após a alta hospitalar. Variáveis com uma frequência >1% na análise bivariada, e que foram consideradas clinicamente significativas, foram qualificadas para análises de modelagens posteriores. A probabilidade posterior de que uma variável estava estatística e significativamente associada ao resultado foi calculada como o número total de vezes em que o IC de 95% da variável não coincidiu com 1 (ou seja, o ponto de referência), dividido pelo número total de iterações. Uma variável com uma probabilidade de 0,9 ou mais alta foi considerado um fator de risco robusto para prever o resultado, e foi incluída na lista final de variáveis. O nível de significância estatística adotado foi 5%. RESULTADOS: Cinco variáveis que pudessem prever de maneira robusta a mortalidade um ano após a alta hospitalar foram identificadas: idade, sexo feminino, escore da New York Heart Association (Associação de Cardiologia de Nova Iorque) >3, diâmetro do átrio esquerdo, e índice de massa corporal. Os modelos de derivação e de teste tiveram uma área de curva característica de operação do receptor de 0,79. Essas variáveis selecionadas foram utilizadas para avaliar o escore de risco de mortalidade por IC após um ano, e este foi dividido em três grupos (baixo, moderado e alto). O grupo de alto risco corresponde a aproximadamente 86% das mortes, e o grupo de risco moderado corresponde a 12% das mortes. CONCLUSÃO: Um escore de risco de 5 variáveis simples pode ser utilizado para avaliar a mortalidade um ano após a alta hospitalar de pacientes internados com IC.

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ABSTRACT Purpose: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). Materials and Methods: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. Results: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. Conclusions: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

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PURPOSE: Epidemiological studies reported conflicting results about preoperative hydronephrosis in upper tract urothelial carcinoma (UTUC). This study aimed to investigate the association between preoperative hydronephrosis and pathologic features and oncologic outcomes in patients with UTUC treated by radical nephroureterectomy (RNU). MATERIALS AND METHODS: This was a retrospective, single-center cohort study of 377 patients treated by RNU without perioperative chemotherapy between January 2001 and December 2014. Logistic regression, Cox regression, and survival analyses were performed. RESULTS: Among the 226 patients with high-grade UTUC, 132 (58%) had preoperative hydronephrosis. Multivariable logistic regression revealed that hydronephrosis was independently associated with advanced pT stage (P=0.017) and lymph node or lymphovascular invasion (P=0.002). Median follow-up was 36 months (interquartile range: 20-48 months). The 3- and 5-year overall survival (OS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P <0.001). The 3- and 5-year cancer-specific survival (CSS) rates in patients with hydronephrosis were significantly lower than in those without hydronephrosis (both P=0.001). Hydronephrosis was independently associated with OS and CSS (P=0.001 and P=0.004, respectively). Among the 151 patients with low-grade UTUC, hydronephrosis was not associated with pathologic features and postoperative survival. CONCLUSIONS: Preoperative hydronephrosis was significantly associated with adverse pathologic features and postoperative survival in patients with high-grade UTUC.

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Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. Ethanol extract of Antrodia cinnamomea (EEA) has been widely studied for its health benefits including anticancer effects. The purpose of this study was to assess the effects of EEA on HNSCC. Cell proliferation, transwell, and wound healing assays were performed. The impact of EEA on tumor growth was investigated using a xenograft model. Expressions of migration-related proteins (MMP-2, MMP-9, TIMP-1, and TIMP-2) and apoptosis-related proteins (cleaved caspase-9 and cleaved PARP) were determined using western blot analysis. The results indicated that EEA significantly inhibited the capacities of proliferation, invasion, and migration of HNSCC cells in a dose-dependent manner. Cleaved caspase-9 and cleaved PARP expressions were increased in cells treated with an increasing concentration of EEA, which suggested that EEA induced apoptosis of HNSCC. MMP-2 and MMP-9 were downregulated when cells were administered EEA, while TIMP-1 and TIMP-2 were not affected, which uncovered the mechanisms mediating the EEA-induced inhibition on cell invasion and migration. The animal experiment also suggested that EEA inhibited tumor growth. Our study confirmed the inhibitive effects of EEA on cell proliferation, invasion, and migration of HNSCC in vitro and in vivo, providing the basis for further study of the application of EEA as an effective candidate for cancer treatment.

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OBJECTIVES: Cognitive decline and gait speed slowing are independent predictors of disability and mortality. While both factors increase in prevalence with advancing age, little is known about their combined patterns of change. The study goal was to identify joint trajectories of cognition and gait speed within an aging bi-ethnic cohort of Mexican Americans and European Americans. METHODS/DESIGN: Participants included 182 Mexican Americans and 188 European Americans, ages 65 to 74, who were followed over a mean of 9.5 years. Cognition was assessed with the mini-mental state examination and gait speed was examined with a timed 10-ft walk. Joint trajectory classes of cognition and gait speed were identified with latent growth mixture modeling. Odd-ratios assessed predictors for trajectory classes. RESULTS: Three latent trajectory classes were identified: (a) relatively stable cognition and gait (termed stable cognition and gait class, 65.4%); (b) deteriorating cognition and gait (termed cognitive and physical vulnerability class, 22.2%); (c) stable cognition and deteriorating gait (termed physical vulnerability class, 12.4%). The odds of classification in the cognitive and physical vulnerability class vs stable cognition and gait class was associated with Mexican American ethnicity (OR = 3.771, P = .016), age (OR = 1.186, P = .017), income (OR = 0.828, P = .029), education (OR = 0.703, P < .001), and diabetes (OR = 4.547, P = .010). The odds of classification in the physical vulnerability class was associated with female sex (OR = 6.481, P = .004) and body mass index (OR = 1.118, P = .025). CONCLUSIONS: The trajectories of cognition and gait speed were generally parallel, suggesting the two domains may act synergistically to shape important health outcomes. Socioeconomic disparities and Mexican American ethnicity independently conferred risk for accelerated decline.

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Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors. Ethanol extract of Antrodia cinnamomea (EEA) has been widely studied for its health benefits including anticancer effects. The purpose of this study was to assess the effects of EEA on HNSCC. Cell proliferation, transwell, and wound healing assays were performed. The impact of EEA on tumor growth was investigated using a xenograft model. Expressions of migration-related proteins (MMP-2, MMP-9, TIMP-1, and TIMP-2) and apoptosis-related proteins (cleaved caspase-9 and cleaved PARP) were determined using western blot analysis. The results indicated that EEA significantly inhibited the capacities of proliferation, invasion, and migration of HNSCC cells in a dose-dependent manner. Cleaved caspase-9 and cleaved PARP expressions were increased in cells treated with an increasing concentration of EEA, which suggested that EEA induced apoptosis of HNSCC. MMP-2 and MMP-9 were downregulated when cells were administered EEA, while TIMP-1 and TIMP-2 were not affected, which uncovered the mechanisms mediating the EEA-induced inhibition on cell invasion and migration. The animal experiment also suggested that EEA inhibited tumor growth. Our study confirmed the inhibitive effects of EEA on cell proliferation, invasion, and migration of HNSCC in vitro and in vivo, providing the basis for further study of the application of EEA as an effective candidate for cancer treatment.

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ABSTRACT Objective Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet β-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. Subjects and methods We conducted a cross-sectional study to compare islet β-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. Results We found that compared with that in normal controls, HOMA-β in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-β in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). Conclusions There were obvious decreases in HOMA-β and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.

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OBJECTIVE: Type 2 diabetes (T2DM) is characterized by the progressive deterioration of pancreatic islet ß-cell function over time and insulin resistance. Knowing more about the differences in pancreatic islet function in T2DM patients who have had diabetes for different lengths of time can help improve therapy for T2DM. SUBJECTS AND METHODS: We conducted a cross-sectional study to compare islet ß-cell function and insulin resistance in T2DM patients (n = 3,254) who had had diabetes for different lengths of time and those in normal controls (n = 794) using ANOVA and LSD analysis. RESULTS: We found that compared with that in normal controls, HOMA-ß in T2DM patients with a history of diabetes of less than 1 year was lower (approximately 52% of that of normal controls, p = 0.003), while HOMA-IR in these patients was higher (approximately 50% of that of normal controls, p = 0.007). Compared with that in other diabetic patients, HOMA-ß in patients with a history of diabetes of more than 30 years was the lowest. HOMA-IR in patients with a history of diabetes of between 20 and 30 years was lower than that in other diabetic patients (p < 0.05). CONCLUSIONS: There were obvious decreases in HOMA-ß and increases in HOMA-IR in T2DM patients with a history of diabetes of less than 1 year compared with those in normal controls. Therefore, early screening and intervention for T2DM might help improve islet function and delay the progression of diabetes.

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BACKGROUND: This study aims to investigate the expression of Id-1 in human colorectal adenocarcinoma tissues and explore its correlation with the clinical pathological parameters of colorectal cancer. METHODS: The Id-1 mRNA and protein expression levels of 50 specimens of normal colorectal tissues and 50 specimens of colorectal adenocarcinoma tissues were detected using reverse-transcription polymerase chain reaction and western blot. Furthermore, Id-1 protein was detected using immunohistochemistry. The correlation between the expression of Id-1 and clinicopathologic features was analyzed. RESULTS: The mRNA expression level of Id-1 in colorectal adenocarcinoma tissues and normal colorectal tissues was 0.96 ± 0.03 vs. 0.20 ± 0.04, respectively; and the difference was statistically significant (P=0.011). Furthermore, Id-1 protein expression was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (0.82 ± 0.04 vs. 0.31 ± 0.02, P=0.020). In addition, the positive protein expression rate of Id-1 was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (72.00% vs. 24.00%, X2=23.431, P=0.000). The expression of Id-1 was correlated with the depth of tumor invasion, TNM stage, lymph node metastasis, vessel invasion, and liver metastasis (P<0.01). However, this expression was not correlated with tumor size and differentiation degrees (P>0.05). CONCLUSIONS: The high Id-1 expression in colorectal adenocarcinoma tissues play an important role in the process of cancer, and is expected to become a new tumor monitoring indicator for clinical diagnosis, treatment, and prognosis judgment.

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SUMMARY BACKGROUND: This study aims to investigate the expression of Id-1 in human colorectal adenocarcinoma tissues and explore its correlation with the clinical pathological parameters of colorectal cancer. METHODS: The Id-1 mRNA and protein expression levels of 50 specimens of normal colorectal tissues and 50 specimens of colorectal adenocarcinoma tissues were detected using reverse-transcription polymerase chain reaction and western blot. Furthermore, Id-1 protein was detected using immunohistochemistry. The correlation between the expression of Id-1 and clinicopathologic features was analyzed. RESULTS: The mRNA expression level of Id-1 in colorectal adenocarcinoma tissues and normal colorectal tissues was 0.96 ± 0.03 vs. 0.20 ± 0.04, respectively; and the difference was statistically significant (P=0.011). Furthermore, Id-1 protein expression was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (0.82 ± 0.04 vs. 0.31 ± 0.02, P=0.020). In addition, the positive protein expression rate of Id-1 was higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (72.00% vs. 24.00%, X2=23.431, P=0.000). The expression of Id-1 was correlated with the depth of tumor invasion, TNM stage, lymph node metastasis, vessel invasion, and liver metastasis (P<0.01). However, this expression was not correlated with tumor size and differentiation degrees (P>0.05). CONCLUSIONS: The high Id-1 expression in colorectal adenocarcinoma tissues play an important role in the process of cancer, and is expected to become a new tumor monitoring indicator for clinical diagnosis, treatment, and prognosis judgment.

RESUMO OBJETIVO: O objetivo deste estudo é investigar a expressão de Id-1 em tecidos de adenocarcinoma colorretal em humanos e investigar sua correlação com os parâmetros patológicos clínicos de câncer colorretal. MÉTODOS: Os níveis de expressão de proteína e mRNA Id-1 em 50 amostras de tecido colorretal normal e 50 amostras de tecido de adenocarcinoma colorretal foram detectados através de reação em cadeia de polimerase precedida de transcrição reversa e western blot. Além disso, a proteína Id-1 foi detectada através de imuno-histoquímica. A correlação entre a expressão de Id-1 e características clínico-patológicas foi analisada. RESULTADOS: O nível de expressão de mRNA Id-1 em tecidos de adenocarcinoma colorretal e tecidos colorretais normais foi de 0,96 ± 0,03 versus 0,20 ± 0,04, respectivamente; a diferença foi estatisticamente significativa (P= 0,011). Além disso, a expressão da proteína Id-1 foi maior em tecidos de adenocarcinoma colorretal do que em tecidos colorretais normais (0,82 ± 0,04 versus 0,31 ± 0,02, P= 0,020). Além disso, a taxa de expressão positiva de proteínas Id-1 foi maior em tecidos de adenocarcinoma colorretal do que em tecidos colorretais normais (72,00% vs. 24,00%, X2=23,431, p=0,000). A expressão de Id-1 foi correlacionada com a profundidade da invasão tumoral, estágio TNM, metástases linfonodais, invasão vascular e metástase hepática (P<0,01). Todavia, essa expressão não se correlacionou com o tamanho do tumor e graus de diferenciação (P>0,05). CONCLUSÃO: A alta expressão de Id-1 em tecidos de adenocarcinoma colorretal desempenham um importante papel no processo do câncer, e é esperado que se torne um novo indicador de monitoramento de tumores para o diagnóstico clínico, tratamento e estimativa de prognóstico.

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OBJECTIVE: To evaluate the safety of adalimumab in pediatric patients who participated in clinical trials of juvenile idiopathic arthritis (polyarticular juvenile idiopathic arthritis and pediatric enthesitis-related arthritis), psoriasis, and Crohn's disease. STUDY DESIGN: This analysis included data from 7 global, randomized, and open-label AbbVie-sponsored clinical trials of adalimumab and their open-label extensions conducted between September 2002 and December 31, 2015 (cutoff date for ongoing studies). Patients who received ≥1 dose of adalimumab subcutaneously were included. Adverse events that occurred after the first dose of adalimumab and up to 70 days (5 half-lives) after the last dose were reported and events per 100 patient-years were calculated. RESULTS: The analysis included 577 pediatric patients, representing 1440.7 patient-years of adalimumab exposure. Across indications, the most commonly reported adverse events (events/100 patient-years) were upper respiratory tract infections (24.3), nasopharyngitis (17.3), and headache (19.9). Serious infections (4.0 events/100 patient-years) were the most frequent serious adverse events across indications; the most commonly reported was pneumonia (0.6 events/100 patient-years). Serious infection rates were 2.7, 0.8, and 6.6 events/100 patient-years in patients with juvenile idiopathic arthritis, psoriasis, and Crohn's disease, respectively. No events of malignancies were reported. One death (accidental fall) occurred in a patient with psoriasis. CONCLUSIONS: The safety profile of adalimumab in pediatric patients with polyarticular juvenile idiopathic arthritis, enthesitis-related arthritis, psoriasis, and Crohn's disease was generally similar across indications; no new safety signals were identified in the treatment of pediatric patients with adalimumab. TRIAL REGISTRATION: Clinicaltrials.gov: NCT00048542, NCT00775437, NCT00690573, NCT01166282, NCT01251614, NCT00409682, and NCT00686374.

RESUMO

BACKGROUND: DNA barcoding has demonstrated that many discrete phenotypes are in fact genetically distinct (pseudo)cryptic species. Genetically identical, isogenic individuals, however, can also express similarly different phenotypes in response to a trigger condition, e.g. in the environment. This alternative explanation to cryptic speciation often remains untested because it requires considerable effort to reject the hypothesis that the observed underlying genetic homogeneity of the different phenotypes may be trivially caused by too slowly evolving molecular markers. The widespread squat lobster Munida gregaria comprises two discrete ecotypes, gregaria s. str. and subrugosa, which were long regarded as different species due to marked differences in morphological, ecological and behavioral traits. We studied the morphometry and genetics of M. gregaria s. l. and tested (1) whether the phenotypic differences remain stable after continental-scale sampling and inclusion of different life stages, (2) and whether each phenotype is underpinned by a specific genotype. RESULTS: A total number of 219 gregaria s. str. and subrugosa individuals from 25 stations encompassing almost entire range in South America were included in morphological and genetic analyses using nine unlinked hypervariable microsatellites and new COI sequences. Results from the PCA and using discriminant functions demonstrated that the morphology of the two forms remains discrete. The mitochondrial data showed a shallow, star-like haplotype network and complete overlap of genetic distances within and among ecotypes. Coalescent-based species delimitation methods, PTP and GMYC, coherently suggested that haplotypes of both ecotypes forms a single species. Although all microsatellite markers possess sufficient genetic variation, AMOVA, PCoA and Bayesian clustering approaches revealed no genetic clusters corresponding to ecotypes or geographic units across the entire South-American distribution. No evidence of isolation-by-distance could be detected for this species in South America. CONCLUSIONS: Despite their pronounced bimodal morphologies and different lifestyles, the gregaria s. str. and subrugosa ecotypes form a single, dimorphic species M. gregaria s. l.. Based on adequate geographic coverage and multiple independent polymorphic loci, there is no indication that each phenotype may have a unique genetic basis, leaving phenotypic plasticity or localized genomic islands of speciation as possible explanations.